Multicenter evaluation of efficacy and toxicity of venetoclax‐based combinations in patients with accelerated and blast phase myeloproliferative neoplasms

King, Amber C.; Weis, Taylor M; Derkach, Andriy; Ball, Somedeb; Pandey, Manu R.; Mauro, Michael J.; Goldberg, Aaron D; Stahl, Maximilian; Famulare, Christopher; Tallman, Martin S.; Wang, Eunice S.; Kuykendall, Andrew; Rampal, Raajit K.

doi:10.1002/ajh.26381

Cited by 17 publications

(11 citation statements)

References 5 publications

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“…7 In another multicentre series of MPN-BP treated with venetoclax based regimens, 28% had documented infections and 19% grade 3 hemorrhage. 8 The differences in adverse event rates between our study and others are possibly a result of differences in treatment regimens. In the current study, response was superior in TET2 mutated patients without antecedent PV.…”

Section: Lists Characteristics Of 47mentioning

confidence: 51%

“…The current series, which is the largest compilation of Ven+HMA treated patients with MPN-BP, serves to expand and refine our prior observations, 3,4 and differs from other reports in terms of exclusion of venetoclax based regimens with cytarabine or cladribine and patients with MPN in accelerated phase. 7,8 The high complete response rate (43%) observed with Ven+HMA was comparable to response following intensive AML induction chemotherapy (CR/CRi 59%). 1 In a phase 2 study of ruxolitinib plus decitabine in patients with either MPN-BP or accelerated phase MPN, overall response rate was 44% (CR/CRi/partial remission (PR) of 0%, 8% and 36%, respectively) per the modified Cheson criteria.…”

Section: Lists Characteristics Of 47mentioning

confidence: 90%

mentioning

confidence: 99%

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Predictors of response to venetoclax plus hypomethylating agent therapy and survival in blastphase myeloproliferative neoplasm

Gangat¹,

Ilyas²,

McCullough³

et al. 2022

haematol

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Section: Lists Characteristics Of 47mentioning

confidence: 51%

Section: Lists Characteristics Of 47mentioning

confidence: 90%

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Predictors of response to venetoclax plus hypomethylating agent therapy and survival in blastphase myeloproliferative neoplasm

Gangat¹,

Ilyas²,

McCullough³

et al. 2022

haematol

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“…Recent studies in MPN-BP have focused on less intensive HMA-based treatment approaches with the goal of attaining CR/CRi, in order to transition to AHSCT. 144 Accordingly, HMA was combined with venetoclax [144][145][146] or ruxolitinib; 141,147 in a Myeloproliferative Neoplasms Research Consortium phase-2 study of 25 patients with MPN-BP or MPN-AP, treated with ruxolitinib-HMA, a CR/CRi rate of 8.1% was reported. 141 By contrast, the CR/CRi rate in a retrospective study of 47 patients with MPN-BP treated with Venetoclax-HMA was reported at 43% and was higher than historically documented for HMA alone.…”

Section: Blast Phase Myeloproliferative Neoplasmmentioning

confidence: 99%

Primary myelofibrosis: 2023 update on diagnosis, risk‐stratification, and management

Tefferi

2023

American J Hematol

115

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Disease Overview Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell‐derived clonal myeloproliferation that is often but not always accompanied by JAK2, CALR, or MPL mutations; additional features include bone marrow reticulin/collagen fibrosis, aberrant inflammatory cytokine expression, anemia, hepatosplenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, risk of leukemic progression, and shortened survival. Diagnosis Bone marrow examination with cytogenetic and mutation studies provides integrated diagnostic information; presence of JAK2, CALR or MPL mutation is expected but not required. New Classification System The International Consensus Classification distinguishes “prefibrotic” from “overtly fibrotic” PMF; the former might mimic essential thrombocythemia (ET) in its presentation. Approximately 15% of patients with ET or polycythemia vera (PV) might progress into post‐ET/PV MF. Mutations SRSF2, ASXL1, and U2AF1‐Q157 mutations predict inferior survival in PMF; RAS/CBL mutations predict resistance to ruxolitinib therapy. Type 1/like CALR mutation is associated with superior survival. Karyotype Very high‐risk abnormalities include −7, inv (3), i(17q), +21, +19, 12p‐ and 11q‐. Favorable risk abnormalities include normal karyotype or isolated +9, 13q‐, 20q‐, 1q abnormalities and loss of Y chromosome. Risk Stratification Contemporary prognostic systems include GIPSS (genetically‐inspired prognostic scoring system) and MIPSS70+ version 2.0 (MIPSSv2; mutation‐and karyotype‐enhanced international prognostic scoring system). GIPSS is based exclusively on mutations and karyotype; MIPSSv2 includes, in addition, clinical risk factors. Risk‐Adapted Therapy Observation alone is advised for MIPSSv2 “low” and “very low” risk disease (estimated 10‐year survival 56%–92%); allogeneic hematopoietic stem cell transplant (AHSCT) is the preferred treatment of choice for “very high” and “high” risk disease (estimated 10‐year survival 0–13%), as well as in carefully selected patients with intermediate‐risk disease (estimated 10‐year survival 30%). Drug therapy in MF is currently palliative and targets anemia, splenomegaly, and constitutional symptoms. JAK2 Inhibitors Ruxolitinib, fedratinib, and pacritinib are FDA approved and respectfully utilized in patients failing treatment with hydroxyurea, ruxolitinib, or with platelet count <50 × 10 (9)/L. Momelotinib is another JAK2 inhibitor that is poised for approval sometime in 2023 and has shown erythropoietic benefits, in addition to affecting spleen and symptom responses. Other Treatment Modalities Splenectomy is considered for drug‐refractory splenomegaly and involved field radiotherapy for non‐hepatosplenic EMH and extremity bone pain. New Directions New agents, alone or in combination with ruxolitinib, are currently under clinical trial investigation (ClinicalTrials.gov) and preliminary results were presented at the 2022 ASH annual meeting and highlighted in the current review.

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“…Accordingly, recent efforts have focused on less intensive treatment approaches with the goal of attaining CR/CRi, to transition to ASCT, without subjecting patients to complications associated with standard AML-like induction therapy. 28 In this regard, HMA-based combinations withVen [28][29][30] or ruxolitinib 24,31 have been evaluated; in a Myeloproliferative Neoplasms Research Consortium phase-2 study of 25 patients with MPN-BP or MPN-AP, treated with Ven-ruxolitinib, a CR/CRi rate of only 8.1% was reported. 24 By contrast, the CR/CRi rate in a retrospective study of 47 patients with MPN-BP treated with Ven-HMA was reported at 43% and was higher than historically documented for HMA alone.…”

mentioning

confidence: 99%

Blast phase myeloproliferative neoplasm: Transplant to the rescue

Tefferi

Bacigalup

2023

American J Hematol

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Multicenter evaluation of efficacy and toxicity of venetoclax‐based combinations in patients with accelerated and blast phase myeloproliferative neoplasms

Cited by 17 publications

References 5 publications

Predictors of response to venetoclax plus hypomethylating agent therapy and survival in blastphase myeloproliferative neoplasm

Predictors of response to venetoclax plus hypomethylating agent therapy and survival in blastphase myeloproliferative neoplasm

Primary myelofibrosis: 2023 update on diagnosis, risk‐stratification, and management

Blast phase myeloproliferative neoplasm: Transplant to the rescue

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